1. Field of the Invention
The present invention relates generally to methods and compositions for the dry powder formulation of cytokines, especially interferons. More particularly, the present invention relates to the spray drying of interferons (IFNs) to produce dry powder formulations of high potency.
2. Description of the Background Art
Interferons are cytokines useful in the treatment of a variety of human diseases ranging from cancer to immune system enhancement. Interferons are commonly formulated as isotonic aqueous solutions for parenteral administration. Recently, clinicians have sought alternative routes of administration for interferons more suitable to long term use by patients. Particularly, aerosol formulations of interferons have been produced for pulmonary delivery as described in WO 91/16038. The formulation is dispersed by volatilization of a liquid propellent. The patent teaches adding a surfactant or the like to improve the dispersibility of a human interferon from a freon delivery system.
Methods and compositions for the preparation of solid polypeptide microparticles as a pharmaceutical aerosol formulation are disclosed in WO 91/16038 wherein IFN-beta was prepared in dry powder form by lyophilizing an aqueous solution of IFN and jet milling following lyophilization. The purification of proteins of molecular weight in excess of 12,000, including human IFN is disclosed in U.S. Pat. No.: 4,503,035. Low pH pharmaceutical compositions of recombinant IFN-beta are disclosed in WO 89/05158.
Because interferons are fairly expensive compounds, it is highly desirable to have formulations of high potency with improved flow characteristics that can be used with high efficiency in dry powder inhalers to produce reproducible doses for pulmonary delivery.
An object of the present invention is to provide an interferon-containing composition suitable for long-term pulmonary administration to a patient in need thereof. Another object of this invention is to provide an interferon-containing powdered composition that is administered by inhalation in a manner that is free of a liquid propellant such as a "FREON" or carbon dioxide.
Another object of this invention is to provide an interferon-containing powdered composition that can be easily manufactured by a method that maintains a high percentage of interferon activity.
Still another object of this invention is to provide an interferon-containing composition that exhibits a high level of stability of the interferon over time.
Other objects may be apparent to one of ordinary skill upon reviewing the following specification and claims.